Oral steroids for nasal polyps

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Oct 11, 2010 - netic resonance imaging (MRI) scan and on nasoendoscopy. Study personnel were blinded to the treatment/placebo groups as well.
Oral steroids for nasal polyps (Review) Martinez-Devesa P, Patiar S

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 7 http://www.thecochranelibrary.com

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . WHAT’S NEW . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW INDEX TERMS . . . . . . . . . . . . . . .

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Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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[Intervention Review]

Oral steroids for nasal polyps Pablo Martinez-Devesa1 , Shalini Patiar2 1 ENT

Department, John Radcliffe Hospital - West Wing, Oxford, UK. 2 Cancer Research UK, Molecular Oncology Laboratories, Oxford, UK Contact address: Pablo Martinez-Devesa, ENT Department, John Radcliffe Hospital - West Wing, Headley Way, Oxford, OX3 9DU, UK. [email protected]. Editorial group: Cochrane Ear, Nose and Throat Disorders Group. Publication status and date: New search for studies and content updated (conclusions changed), published in Issue 7, 2011. Review content assessed as up-to-date: 11 October 2010. Citation: Martinez-Devesa P, Patiar S. Oral steroids for nasal polyps. Cochrane Database of Systematic Reviews 2011, Issue 7. Art. No.: CD005232. DOI: 10.1002/14651858.CD005232.pub3. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background This is an update of a Cochrane Review first published in The Cochrane Library in Issue 1, 2007. Benign nasal polyps are lesions that arise from the mucosa of the nasal cavity or one or more of the nasal sinuses. The presenting symptoms are nasal obstruction, watery anterior rhinorrhoea (excessive nasal secretions) or mucopurulent postnasal drip (or both), hyposmia and anosmia (reduced or absent sense of smell) with a concomitant alteration in taste and infrequently pain over the dorsum of the nose, forehead and cheeks. The main aim of treatment is to relieve these symptoms. The aetiology of polyps is uncertain, therefore treatment options differ, consisting of a combination of medical and surgical management. Medical therapy is mainly in the form of steroids, administered topically or systemically via the oral route. Objectives To assess the effects of oral steroids in patients with multiple nasal polyps. Search methods We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 12 October 2010, following a previous search in April 2006. Selection criteria Randomised controlled trials and controlled clinical trials comparing oral steroids with no intervention, or placebo, or comparing doses or schedules of oral steroids in patients with multiple nasal polyps. Data collection and analysis Two authors independently assessed study quality. We contacted study authors for additional information. Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Main results Three trials (166 patients) met our inclusion criteria and showed a short-term benefit of a short (two to four-week) course of oral steroids of variable doses and duration when compared to placebo. There was an objective reduction of polyp size and a subjective improvement of nasal symptoms and quality of life. However, due to the moderate to low quality of these trials it was not possible to quantify the overall size of this effect. There was no report of significant adverse effects of treatment with a short course of steroids. Authors’ conclusions The authors found three randomised controlled trials, albeit of moderate to poor quality, that suggest a short-term benefit of oral steroids in patients with multiple nasal polyps. To address the issue more thoroughly well-designed, prospective, randomised controlled trials are still needed.

PLAIN LANGUAGE SUMMARY Oral steroids for nasal polyps Benign nasal polyps are bags of watery tissue arising from the lining (mucosa) of the nasal cavity or the nasal sinuses that protrude into the nasal passages, often on both sides of the nose. The symptoms are nasal obstruction, poor sinus drainage, loss of smell that affects a person’s ability to taste, runny nose or nasal congestion. These can be troublesome or limit daily activities and ability to sleep so that wellbeing and quality of life are reduced. Nasal polyps can be removed surgically or treated with steroid medication, given by nasal sprays or drops (topically) or by mouth (orally). Treatment is either aimed at treating the initial problem or is aimed at preventing recurrence of polyps. No single surgical technique has proved entirely curative and people often undergo repeat procedures. Oral steroids may reduce the need for surgery but there are concerns about possible side effects with long-term oral steroid use. The side effects of short courses of oral steroids are less clearly defined. We found three trials, with a total of 166 patients, that met the inclusion criteria for the review. In these trials the 96 patients who were randomised to receive oral prednisone showed an improvement in quality of life and nasal symptom scores and a significant reduction in polyp size after two to four weeks of treatment compared to no steroid treatment. However, the trials were of moderate to low methodological quality.

BACKGROUND This is an update of a Cochrane Review first published in The Cochrane Library in Issue 1, 2007. Benign nasal polyps are lesions (abnormal changes in structure) that arise from the mucosa of the nasal cavity or one or more of the nasal sinuses, often at the outflow tract of the sinuses. Their aetiology is uncertain, therefore treatment options differ and no one treatment has been found to be universally effective.

Prevalence and incidence There is a higher incidence of polyps in males, with a male-tofemale ratio of between 2:1 and 4:1. They are found in all ethnic

groups although the comparative incidence has not been documented. They predominantly affect adults and usually present in patients over the age of 20 years. In asthmatic patients aged over 40 the prevalence is four times greater than in asthmatic patients under 40 (12.4% versus 3.1%, P < 0.01) (Settipane 1977). They are rare in children under 10 years of age and may be the presenting feature or indicative of cystic fibrosis. The true incidence of nasal polyps is difficult to assess but seems to be far more common in autopsy studies than clinical studies have shown. Endoscopic examination of cadavers revealed nasal polyps in 22 out of 69 autopsies without a history of previous sinonasal disease, with most of the polyps originating from the mucosa of the ostia, clefts and recesses in the osteomeatal complex (the region that drains the sinuses) (Larsen 2004). This is where the initial stage of sinonasal polyposis seems to take place.

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Aetiology

Treatment

The aetiology of nasal polyps is unknown. Most theories consider polyps a consequence of chronic inflammation and therefore conditions leading to chronic inflammation in the nasal cavity can lead to nasal polyps. The medical conditions most notably associated with polyps are non-allergic asthma, aspirin hypersensitivity and cystic fibrosis. Nasal polyps are found in 36% of patients with aspirin intolerance, 7% of those with asthma and about 20% of those with cystic fibrosis (Settipane 1996). No evidence exists, however, for an allergic origin (Drake-Lee 1984). In allergic rhinitis the prevalence of symptomatic nasal polyps is low (1.5%) and similar to that in the normal population (1%) (Lund 1995). Polyps are statistically more common in non-allergic asthma than allergic asthma (13% versus 5%, P < 0.01) (Settipane 1996). There is a well-recognised subgroup of patients with aspirin hypersensitivity and asthma, this subgroup comprising 5% to 10% of patients with nasal polyps.

Treatment of nasal polyps is a combination of medical and surgical management dependent on individual patient assessment. The aims of treatment are to relieve nasal obstruction, restore olfaction, improve sinus drainage and to treat any accompanying rhinitic symptoms (Scadding 2002). Treatment may be divided into two areas: primary (inducing remission) and secondary (preventing recurrence). No single surgical technique has proved entirely curative and patients often undergo repeat procedures and receive long-term medical treatment. Recurrence is common and between 5% and 10% of patients have recurrent severe disease (Drake-Lee 2004). About 60% of patients will require a further polypectomy in a five-year period, the rest having less frequent recurrences (Larsen 1997). There are few direct comparisons of medical and surgical treatment in the literature. Those that exist suggest that most patients should be treated medically, with surgery reserved for patients who respond poorly. The surgical management of nasal polyps has changed over the last two decades with the advent of endoscopic sinus surgery. Intranasal surgery for nasal polyps ranges from simple snare polypectomy (surgical removal of nasal polyps using a snare with or without an endoscope) to radical ethmo-fronto-sphenoidectomy (opening and ventilating the frontal, ethmoid and sphenoid sinuses). Major complications of endoscopic surgery are rare but can be devastating, including loss of vision and entering the skull base causing leakage of fluid from around the brain (cerebrospinal fluid leak) (Stammberger 1999). Corticosteroids are the only medical therapy to have a proven effect on the symptoms and signs of nasal polyps and can be used topically or systemically. The therapeutic modality that has been best studied in controlled trials is that of topically applied steroids. This reduces rhinitis symptoms, improves nasal breathing, reduces the size of polyps and the recurrence rate, but has a negligible effect on the sense of smell and on any sinus pathology. Topical steroids can, as maintenance therapy, be used alone in mild cases, or combined with systemic steroids/surgery in severe cases. Systemic steroids, which are less well studied, have an effect on all types of symptoms and pathology, including the sense of smell. This type of treatment is only used for short-term improvement due to the risk of adverse effects (Mygind 1996). The adverse effects of short-term steroid use are said to include glucose intolerance, hypertension, adrenal suppression, gastrointestinal bleeding and altered mental states. However, there are few or no published data on the frequency of these effects. Adverse effects associated with long-term use of oral steroids include gastrointestinal complications, growth suppression, diabetes mellitus, hypertension, psychotropic effects (e.g. mood changes), glaucoma, osteoporosis and avascular osteonecrosis (bone death resulting from poor blood supply to an area of bone). In a recent retrospective review of litigation trends related to the administration of corticosteroids and the reported complications (Nash 2011) it was advised that physicians should obtain informed

Diagnosis Macroscopically polyps appear as pale bags of oedematous tissue arising most commonly from the middle meatus and prolapsing into the nasal cavity. The pale colour is due to poor blood supply but with repeated trauma and inflammation polyps may become reddened and the surface becomes squamous rather than respiratory in type. They are most often bilateral and when unilateral require histological examination to exclude the transitional cell papilloma (also known as Ringert’s tumour or inverted papilloma) or malignancy (Drake-Lee 2004). Histologically polyps are characterised by ciliated columnar epithelium, thickening of the basement membrane, a loose avascular grossly oedematous stroma and an infiltrate of plasma cells and many eosinophils. Eosinophils are found in 85% to 90% of polyps. The majority of the remaining cells in polyps are neutrophils. The main presenting symptom of nasal polyps is nasal obstruction, which is constant, although it will vary with the size and position of polyps. Patients may also complain of watery anterior rhinorrhoea (excessive nasal secretions) or mucopurulent postnasal drip, or both. Hyposmia and anosmia (reduced or absent sense of smell) with a concomitant alteration in taste are characteristic symptoms of nasal polyps. Pain is an infrequent feature but does occur in patients with polyps and is usually over the dorsum of the nose, forehead and cheeks. It is worse when the nose is congested and there is secondary infection of the sinuses (Drake-Lee 1997). The diagnosis is made by rhinoscopy, anterior and posterior. The diagnosis is often easier if a small probe is used for gentle palpation as polyps are insensitive and are mobile on their pedicles. Plain radiographs of the paranasal sinuses are of no value in the diagnosis of nasal polyps although they may confirm opacification of the sinuses. A computed tomogram (CT) shows the anatomical variations and the extent of the disease.

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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consent prior to steroid therapy. However, only three of 83 cases reviewed involved otolaryngologists and the indication and administration route of the steroid treatment was not the one for nasal polyps or other nasal pathology. There are few controlled trials on the effectiveness of oral steroids in the treatment of nasal polyps. Oral steroids are most often used in high dose for short duration in exacerbations of nasal polyposis. There is however a lack of evidence regarding the optimal treatment regimen of oral steroids with respect to indication, dose and duration. The optimum usage of steroids is clinically important as it may reduce the need for surgery by providing good symptomatic control. The 2007 European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2007) supports the use of a short course of oral steroids followed by topical steroids in patients with chronic rhinosinusitis with nasal polyps if the symptoms are severe (visual analogue scale score > 7 on a 0 to 10 scale). This is based on evidence from open studies and two randomised controlled trials (Benitez 2006; Hissaria 2006) (evidence level Ib).

Exclusion criteria

• Children < 16 years • Antrochoanal polyps (benign polyps originating from the mucosa of the maxillary sinus) • Cystic fibrosis • Surgery for nasal polyps within three months prior to study period

Types of interventions • Oral steroids versus no intervention • Oral steroids versus placebo • Oral steroid versus other type of oral steroid, including: ◦ low-dose (equivalent to less than 20 mg prednisolone) versus high-dose oral steroids (equivalent to more than 40 mg prednisolone) ◦ short-course (less than two weeks) versus long-course oral steroids (more than two weeks) • Topical steroids combined with intervention in both treatment arms in all the above

OBJECTIVES Types of outcome measures To assess the effects of oral steroids in patients with multiple nasal polyps. Primary outcomes

METHODS

Criteria for considering studies for this review

Types of studies All identified randomised controlled trials which fulfilled the criteria outlined below were included.

Types of participants

Reduction in validated nasal symptom scores.

Secondary outcomes

• • • • •

Change in nasal endoscopic findings Change in radiological/CT appearance Duration of effect Improvement in validated quality of life measures* Adverse effects

*We added this secondary outcome measure subsequent to publication of the protocol as we considered it to be an important outcome measure which was overlooked at the time of writing the protocol.

Inclusion criteria

Two or more of the criteria below. • Patients with benign bilateral nasal polyps diagnosed clinically in an ENT department • Endoscopic evidence of nasal polyps • Radiological evidence of nasal polyps

Search methods for identification of studies We conducted systematic searches for randomised controlled trials. There were no language, publication year or publication status restrictions. The date of the last search was 12 October 2010, following a previous search update in April 2006.

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Electronic searches

Assessment of risk of bias in included studies

We searched the following databases from their inception for published, unpublished and ongoing trials: the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4); PubMed; EMBASE; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Science; BIOSIS Previews; CNKI; ISRCTN; ClinicalTrials.gov; ICTRP and Google. We modelled subject strategies for databases on the search strategy designed for CENTRAL. Where appropriate, we combined subject strategies with adaptations of the highly sensitive search strategy designed by the Cochrane Collaboration for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2, Box 6.4.b. (Handbook 2009)). Search strategies for major databases including CENTRAL are provided in Appendix 1.

The two review authors assessed the quality of the included trials independently and we resolved any differences in opinion by discussion. We used a modification of the method used by Chalmers 1990. We assessed the selected studies for the following characteristics: 1. the adequacy of the randomisation process; 2. the potential for selection bias after allocation to study group, i.e. losses to follow up and whether analysis was by intention-to-treat; 3. whether there was blinding of outcome assessors to the participants’ study group; and 4. the quality of outcome assessment. Studies were graded A, B or C for their overall methodological quality: A: minimisation of bias in all four categories above, i.e. adequate randomisation; few losses to follow up and intention-to-treat analysis; blinding of outcome assessors; high quality outcome assessment; B: each of the criteria in A partially met; C: one or more of the criteria in A not met.

Searching other resources We scanned the reference lists of identified publications for additional trials and contacted trial authors where necessary. In addition, we searched PubMed, TRIPdatabase, NHS Evidence - ENT & Audiology, and Google to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials. In previous searches in 2006, we contacted authors of published and unpublished trials and other experts in the field but no additional trials were identified.

Data collection and analysis

Selection of studies The two authors reviewed the titles and abstracts, where available, of all studies identified by the searches and applied the inclusion/ exclusion criteria independently. We excluded articles that did not meet the inclusion criteria. We obtained the full articles for those studies that appeared to meet the inclusion criteria or where there were insufficient data to make a decision. Any disagreement about whether a study should be included was resolved by discussion between the review authors.

Data synthesis We did not identify sufficient trials to allow data analysis. Should suitable trials be identified for updates of the review we will employ the following methods: Data analysis will be on an intention-to-treat basis. If data are comparable and of sufficient quality, we will combine data to give a summary measure of effect, otherwise we will not combine data. We will examine statistical heterogeneity by subgroup analysis as appropriate. We will seek statistical advice as necessary.

RESULTS

Description of studies See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.

Results of the search Data extraction and management The review authors independently extracted data from the studies using standardised data forms. We extracted data to allow an intention-to-treat analysis. Where data were missing we wrote to the authors of the study requesting further information.

We considered 30 studies to be possibly relevant based on the abstract and obtained the full articles.

Included studies

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Three trials satisfied the inclusion criteria (Alobid 2006; Hissaria 2006; Van Zele 2010). The methods, participants, interventions and outcomes of these studies are shown in the table of ’Characteristics of included studies’.

Excluded studies Of the 30 studies retrieved in full text, we excluded 25. Fourteen studies looked at the effects of oral steroids with or without topical steroids on nasal polyps but were excluded as they were non-randomised and non-controlled trials (Bonfils 1998; Bonfils 2003; Bonfils 2006; Cassano 1996; Chi Chan 1996; Hessler 2007; Jankowski 2003a; Jankowski 2003b; Nores 2003; Rasp 1997; Rasp 2000; Stevens 2001; Tuncer 2003; van Camp 1994). Two of the papers were duplicate publications and were excluded as they compared intramuscular steroids against surgery (Lildholdt 1988; Lildholdt 1989). Damm 1999 compared two different durations of oral steroid treatment but had to be excluded, despite contacting the authors, as the outcome data were combined for the two groups and were thus not extractable. We excluded Alobid 2005 as it compared oral steroids against endoscopic sinus surgery, as well as Blomqvist 2001 for the same reason. We excluded Blomqvist 2009 as it was a duplicate publication of Blomqvist 2001. We excluded Ragab 2006 as it compared medical therapies not including oral steroids against surgery. Kroflic 2006 compared oral steroids versus topical furosemide and was thus excluded. One randomised controlled trial compared oral steroids against no intervention prior to endoscopic sinus surgery in both groups but only intraoperative surgical outcome measures were reported so the study had to be excluded (Sieskiewicz 2006). We excluded Benitez 2006 as a possible duplication of Alobid 2006. Both studies were carried out in the same department and during the same period of time: February 1999 to July 2003 in Alobid 2006 with 78 participants and February 1999 to November 2003 in Benitez 2006 with 84 patients recruited. The participants’ characteristics were also very similar. The main differences were in the outcome measures and the subdivision of the treatment group into patients with and without asthma in the second study (Benitez 2006). We contacted the (same) corresponding author for both trials but there was no comment on this point. After a discussion between the review authors we decided not to include Benitez 2006 so as to avoid possible bias (duplication of results). We also identified two abstract publications of trials later to be published (Van Zele 2010) or still awaiting publication (Vaidyanathan 2009). We made attempts to obtain unpublished details and data from the latter trial (Vaidyanathan 2009) but were unsuccessful. The summaries of excluded studies are listed in the table of ’ Characteristics of excluded studies’.

Risk of bias in included studies

Selection and performance bias The included studies were randomised and controlled. On attempting to contact the corresponding authors of all three studies, only the corresponding author of Alobid 2006 replied that randomisation was computer-generated on a 1:3 ratio. Van Zele 2010 used randomisation codes. Hissaria 2006 did not explain the method of randomisation (“…patients were randomised by the hospital pharmacy…”). With the exception of Alobid 2006, where of the 78 patients recruited to the study only 18 (23%) were randomised to the control arm, the other studies showed more balanced study arms. Alobid 2006, however, maintained a good proportion in the baseline characteristics of the groups’ population, while Hissaria 2006 had a larger number of males, history of aspirin sensitivity, smokers and subjects that had undergone previous polyp operations in the control (placebo) group. Van Zele 2010 had a larger incidence of asthma and aspirin intolerance also in the placebo group. Concealment assignment was described in Hissaria 2006 and Van Zele 2010. Subjects in both studies were blinded for the whole duration of the study. No information on concealment was provided in Alobid 2006.

Attrition bias Two participants in Alobid 2006 were lost to follow up in the control (placebo) group. One participant dropped out in the placebo group in Hissaria 2006. Seven participants (15%) withdrew from the placebo group before the first observation point in Van Zele 2010.

Detection bias Alobid 2006 did not comment on blinding of assessors. Hissaria 2006 used blind outcome assessors for the physician assessment of nasal symptoms, the assessment of polyp size on magnetic resonance imaging (MRI) scan and on nasoendoscopy. Study personnel were blinded to the treatment/placebo groups as well as pre- and post-treatment observation points in the polyp size assessments with MRI/nasoendoscopy. At the end of the study participants were unblinded by an independent physician and all who had taken placebo accepted were offered and were offered and accepted a course of oral steroids. Van Zele 2010 study personnel were also blinded for the duration of the study. The scales used to measure nasal symptoms score varied significantly: a subset of six nasal symptoms of the Rhinosinusitis Outcome Measure questionnaire (RSOM-31) in Hissaria 2006; a nonvalidated scoring system (0 to 3) in Alobid 2006 and an unclear

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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(possibly 0 to 3 points) scoring system in Van Zele 2010. Overall the assessment of nasal symptoms in the included studies was poor. One study (Hissaria 2006) was graded B for overall methodological quality according to the stated criteria. The other two studies ( Alobid 2006; Van Zele 2010) were graded C.

Effects of interventions Three trials comprising 166 participants were included in this review. We analysed the prespecified primary and secondary outcomes. Primary outcome

Validated nasal symptoms scores

There was significant variation in the assessment of nasal symptoms. Hissaria 2006 used a subset of six nasal symptoms of the Rhinosinusitis Outcome Measure (RSOM-31) questionnaire. The nasal symptom scores were significantly reduced (reduction was considered by an improvement of 20% or more) from before to after two weeks of treatment in the treatment group (50 mg oral prednisolone for 14 days) (64% reduction (P < 0.001)) versus the control (placebo) group (11% reduction (P = non-significant)). There was no long-term follow up in this study. Alobid 2006 also showed a reduction in the scores of nasal symptoms (0 to 3 scoring system): nasal obstruction and loss of sense of smell (P < 0.05) in the treatment group (reducing course of 30 mg oral prednisolone for two weeks) two weeks after commencing treatment compared to the control (no treatment) group. After the first assessment point at two weeks the nasal symptom scores were still lower than at baseline at weeks 12, 24 and 48 in the treatment group. However, the control group was not followed up as due to ethical considerations this group was not kept “without known effective treatment” for longer than six weeks. Van Zele 2010 reported a decrease in nasal congestion at weeks one, two and four after treatment in the treatment group (reducing course of 32 mg to 8 mg of methylprednisolone during 20 days) (week 1, P = 0.002; week 2, P = 0.007; week 4, P = 0.001) compared to the placebo group. Post-nasal drip showed a score reduction in the treatment group versus placebo (week 1, P = 0.31; week 2, P = 0.007 and week 4, P = 0.001). Loss of sense of smell also had a similar score reduction in the treatment group versus placebo (week 1, P = 0.006; week 2, P = 0.001; week 4, P = 0.006). Congestion and other nasal symptom scores worsened progressively after week four and returned to baseline values. There was no significant effect of oral steroid treatment on rhinorrhoea compare to placebo. After week four there were 10 patients (52%) in the placebo group and two patients (14%) in the oral steroid group that needed rescue treatment. There was no long-term assessment.

Secondary outcomes

Change in nasal endoscopic findings

Alobid 2006 showed a significant reduction in endoscopic assessment of polyp size (Lildholt classification, 0 to 3) at week two in the treatment group versus control (P < 0.05) and the polyp size was maintained in the treatment group at weeks 12, 24 and 48 (P < 0.05). Long-term effect was not comparable to the control group. In Hissaria 2006, at week two, there was a reduction in polyp size of 48% (mean change; P < 0.005) compared to placebo. Van Zele 2010 also showed a reduction of polyp size in the treatment group after week one (P = 0.002) that become maximal at week two (P < 0.0001) compared to placebo. There was still a significant reduction in polyp size after two months in the oral steroid group (P < 0.05) compared to placebo but there was no difference of effect after three months.

Change in radiological appearance

There was also a reduction in the magnetic resonance imaging (MRI) score in the treatment group of 45% (P < 0.001) versus placebo in Hissaria 2006 at week two.

Quality of life

Alobid 2006 used the validated Medical Outcome Study Short Form-36 (SF-36; 0 to 100, 100 being the better quality of life score) to assess general quality of life. Both the physical and mental components of SF-36 showed a significant score increase for the treatment group compared to the control group at week two (P < 0.05). This increase was maintained in the treatment group at weeks 12, 24 and 48 (P < 0.05). In Hissaria 2006, RSOM-31 also measured quality of life. There was also a reduction in total RSOM score in both groups but the level of improvement was significantly more in the treatment group (treatment, 53% improvement, P < 0.001 versus placebo 21% improvement, P < 0.005).

Adverse effects

There was no record of adverse events in Alobid 2006 and when we contacted the main author he reported that there were no adverse effects in the trial. Hissaria 2006 reported adverse effects in both treatment and control groups. The main adverse effects were insomnia (in eight participants in the treatment group and two in the placebo group) and mood disturbance (five in the treatment group, two in placebo); and in fewer numbers headache, dyspepsia, increased

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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appetite, fatigue, backache, gastrointestinal disturbance, acne and feet oedema. There were no significant adverse effects. Van Zele 2010 reported that 48.5% of the subjects in the study reported at least one adverse event. There were no significant differences in adverse events between the treatment and placebo groups.

DISCUSSION Our objective in this 2010 update of the review was to assess the effect of oral steroids in the treatment of nasal polyps. Despite a large number of initial references retrieved, only three studies met the inclusion criteria and were in general of moderate to poor methodological quality (Hissaria 2006 grade B; Alobid 2006 and Van Zele 2010 both grade C). Except for Alobid 2006, the format used for presentation of data in the papers and lack of response from the corresponding authors precluded a meta-analysis of the results. Hissaria 2006 and Alobid 2006 both compared treatment with the oral steroid prednisolone at different doses (Hissaria 2006: 50 mg daily for two weeks; Alobid 2006: a reducing course starting at 30 mg per day and reducing gradually during two weeks) versus placebo. The study groups in Hissaria 2006 were more balanced (20 patients each) than in Alobid 2006 (60 patients in the treatment group; 18 in the control group). Two patients were lost in Alobid 2006 and one in Hissaria 2006, in both cases in the placebo group. Both studies showed improvement in the outcome measures. Alobid 2006 continued to measure only the treatment group for up to 48 weeks and the study reported that the improvements on all outcomes measured were maintained during this time. Van Zele 2010 compared three arms in their study: oral steroid (reducing course of methylprednisolone) versus antibiotic (doxycycline) versus placebo. The groups were well-balanced with 14 patients each in the steroid and antibiotic groups and 19 in the placebo group. However, there was a significant dropout of seven patients (15%), all of them in the placebo group, after week four. Up to this point in the study the treatment group showed a significant improvement of most nasal symptoms (nasal congestion, postnasal drip and sense of smell) in the steroid group. Congestion and other nasal symptom scores worsened progressively after week four and returned to baseline values. Oral steroid had no effect on reducing rhinorrhoea when compared to placebo. Interestingly, doxycycline significantly reduced postnasal drip and rhinorrhoea, the former even more than in the steroid group. Polyp size also was reduced in the steroid group when compared to placebo, with maximal reduction after two weeks. Doxycycline also showed a reduction in polyp size. After the four-week assessment point, failure of treatment resulted in rescue treatment for all groups (14% in the steroid group; 28% in antibiotic group and 52% in the placebo group). Although the study continued to assess the longterm outcome measures for all groups, we considered the dropout

and rescue treatment rate inappropriate to include the long-term effect data reported in this study in this review. The individual study results in this review support the positive effect of a short course (and of different doses) of oral steroids in the objective reduction of polyp size and the subjective improvement of nasal symptoms and quality of life. As it was not possible to conduct a meta-analysis we could not quantify the overall size of this effect. There are no data to support the maintenance of this effect in the long term (when compared to placebo) and without this evidence this type of treatment could be relegated to an adjuvant treatment in the management of nasal polyposis. In the studies included in this review there was no report of significant adverse effects of treatment with a short course of steroids. Hissaria 2006 and Van Zele 2010 reported some minor adverse effects in both treatment and placebo groups. In general the evidence from randomised controlled trials or metaanalysis as to the adverse effects of steroids is both scarce and variable. A search through the Cochrane Reviews that compared the use of steroids for the treatment of diverse conditions in adults identified six reviews in which oral steroids were used. Three of these reviews used a dose similar to that used for the treatment of nasal polyps and there were some minor and short-lived adverse effects of oral steroids (Buchbinder 2006; Walters 2005; Wei 2006), however the adverse effect results were somewhat variable. In two of the reviews the reported adverse effects were minor and short-lived (Buchbinder 2006) or did not exist at all (Wei 2006). However, in a third review on the use of oral steroids for chronic obstructive pulmonary disease (COPD) (Walters 2005), the pooled adverse effect from three of the studies in the review (111 participants) showed an odds ratio of a major adverse effect of 7.76 (95% CI 2.34 to 25.70) or one major adverse effect for every nine people treated. In one of the studies included in this review, the reported osteocalcin level was significantly reduced in the oral steroid treatment group. The authors, in their conclusions, warned about the increased risk of adverse effects at doses that are unacceptable in the long term. In the other three reviews (Burton 2009; Cheng 1999; Mash 2001), the dose and/or duration of treatment with oral steroid used was significantly higher than that used for the treatment of nasal polyps and although minor adverse effects were reported there was no information on long-term effect. The common message from all these reviews is that the pros and cons of oral steroid therapy should be considered in individual patients. The conclusions of one of these reviews (Mash 2001) suggested that a systematic review of the side effects of steroids would be necessary to address this issue fully. With regards to the adverse effects of oral steroids specifically in the treatment of nasal polyposis, two non-randomised studies looked

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in particular at the effect on osteopenia and bone density and their results and conclusions may be helpful: One retrospective study (Rajasekaran 2010) looked at 197 patients diagnosed with chronic rhinosinusitis with or without polyposis. The mean age of the patients was 51.1 years (range 15 to 79) and 81.7% had concomitant asthma. The patients had received at least 5 mg of oral steroids daily for at least three months. The authors observed a higher rate of osteopenia/osteoporosis or low bone density (LBD) among men > 50 years of age and postmenopausal women, which was 62.5% and 62.2% respectively. Comparing this population with their respective younger populations there was a statistically significant low bone mass (P < 0.0001) in the older population groups, with an odds ratio of 10.6 (3.9 to 28.7) and 34.6 (7.4 to 161.5) for men > 50 and postmenopausal women respectively. There was no difference on gender. The authors advised careful evaluation and treatment in this older age group to prevent additional bone-related complications. One of the non-randomised excluded studies in this review (Bonfils 2006) reported on adrenal suppression and osteoporosis in a prospective longitudinal study of 46 patients treated for nasal polyposis with repeated short courses (more than 21 days of treatment in total) of oral prednisolone 1 mg/kg body weight. The mean age of the patients was 49.4 (+/- 1.6), 56.5% were male and the mean duration of the treatment was 4.7 years (SD = 4.2) with a mean number of oral steroid courses per year (seven to 10 days duration for each course) of 6.8 (SD = 4.7). Almost 80% of these patients also received intranasal steroids simultaneously. In 48.8% and 12.2% of patients there was osteopenia and osteoporosis (respectively) at the lumbar spine; 43.9% had osteopenia at the femoral neck (none had osteoporosis) and 40.5% and 54% had osteopenia and osteoporosis at the proximal femur. Also 20 of these patients (48.8%) had adrenal insufficiency on synacthen test but only one patient was symptomatic. The authors of this study concluded that patients with severe nasal polyposis and a high steroid consumption have a high prevalence of glucocorticoid-induced osteoporosis and secondary adrenal insufficiency. They concluded that patients should be informed of the risks and monitored during long-term steroid treatment. In summary, the evidence relating to a short course of a moderate dose of oral steroids indicates that is safe, although very few studies have looked at the effect on osteopenia and bone density and secondary adrenal insufficiency. The studies that looked at these parameters do report a high prevalence of osteoporosis and secondary adrenal insufficiency. In conclusion there is a lack of strong evidence for significant adverse effect/s of oral steroids for the treatment nasal polyps. We concur with the consensus opin-

ion that the balance of risks and benefits of oral steroid therapy should be carefully considered in each individual patient and that this information should be conveyed to the patient as part of the informed choice regarding their treatment. A short course of oral steroids could be beneficial in the short term to patients with nasal polyps (provided there are no contraindications).

AUTHORS’ CONCLUSIONS Implications for practice A limited number of trials of moderate to poor methodological quality showed a short-term improvement with a short (two to four-week) and variable dose course of oral steroids in the treatment of nasal polyps. The trials showed improvement in the objective reduction of polyp size and the subjective improvement of nasal symptoms and quality of life. It was not possible to quantify the overall size of this effect. Without long-term supporting data, there is no evidence of a sustained effect of this treatment and without this evidence this type of treatment could be relegated to an adjuvant treatment in the management of nasal polyposis. There were reports of some adverse events in the included trials but no significant adverse effects of treatment with a short course of steroids were reported.

Implications for research There is still a need for trials of high methodological quality on the use of oral steroids for the treatment of nasal polyps. Longer follow up is necessary to establish the long-term effect of this intervention. The presence or absence of adverse effects of treatment with oral steroids should always be reported in a standardised manner with short and long-term measures.

ACKNOWLEDGEMENTS The authors would like to thank the staff of the Cochrane ENT Group for their help in producing this review, particularly Gemma Sandberg for development of the search strategy and searching for trials.

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REFERENCES

References to studies included in this review Alobid 2006 {published data only} Alobid I, Benitez P, Pujols L, Maldonado M, BernalSprekelsen M, Morello A, et al.Severe nasal polyposis and its impact on quality of life. The effect of a short course of oral steroids followed by long-term intranasal steroid treatment. Rhinology 2006;44(1):8–13. Hissaria 2006 {published data only} Hissaria P, Smith W, Wormald PJ, Taylor J, Vadas M, Gillis D, et al.Short course of systemic corticosteroids in sinonasal polyposis: a double-blind, randomized, placebo-controlled trial with evaluation of outcome measures. Journal of Allergy and Clinical Immunology 2006;118(1):128–33. Van Zele 2010 {published data only} Van Zele T, Gevaert P, Holtappels G, Achim B, Wormald P, Mayr S, et al.Treatment of nasal polyposis with oral methylprednisolone: a double-blind, randomized, placebocontrolled trial with evaluation of clinical and biological activity. American Academy of Allergy, Asthma and Immunology (AAAAI) 64th Annual Meeting. Philadelphia, PA, USA, March 14-18, 2008. Journal of Allergy and Clinical Immunology. 2008; Vol. 121 (2 (Suppl 1)):S265, Abstract No. 1028. ∗ Van Zele T, Gevaert P, Holtappels G, Beule A, Wormald PJ, Mayr S, et al.Oral steroids and doxycycline: two different approaches to treat nasal polyps. Journal of Allergy and Clinical Immunology 2010;125(5):1069–76.

References to studies excluded from this review Alobid 2005 {published data only} Alobid I, Benitez P, Bernal-Sprekelsen M, Roca J, Alonso J, Picado C, et al.Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments. Allergy 2005;60(4):452–8. Benitez 2006 {published data only} Benitez P, Alobid I, de Haro J, Berenguer J, Bernal Sprekelsen M, Pujols L, et al.A short course of oral prednisone followed by intranasal budesonide is an effective treatment of severe nasal polyps. Laryngoscope 2006;116(5): 770–5. Blomqvist 2001 {published data only} Blomqvist EH, Lundblad L, Anggard A, Haraldsson PO, Stjarne P. A randomised controlled study evaluating medical treatment versus surgical treatment in addition to medical treatment of nasal polyposis. Journal of Allergy and Clinical Immunology 2001;107(2):224–8. Blomqvist 2009 {published data only} Blomqvist EH, Lundblad L, Bergstedt H, Stjarne P. A randomized prospective study comparing medical and medical-surgical treatment of nasal polyposis by CT. Acta Oto-Laryngologica 2009;129(5):545–9.

Bonfils 1998 {published data only} Bonfils P. Medical treatment of paranasal sinus polyposis: a prospective study in 181 patients [Le traitement medical de la polypose naso–sinusienne: etude prospective sur une serie de 181 patients]. Annales d’Oto-Laryngologie et de Chirurgie Cervico Faciale 1998;115(4):202–14. Bonfils 2003 {published data only} Bonfils P, Nores J-M, Halimi P, Avan P. Medical treatment of stage I nasal polyposis over a 3-year follow-up period. ORL 2004;66(1):27–34. Bonfils 2006 {published data only} Bonfils P, Halimi P, Malinvaud D. Adrenal suppression and osteoporosis after treatment of nasal polyposis. Acta OtoLaryngologica 2006;126(11):1195–200. Cassano 1996 {published data only} Cassano P, Marini F, Indraccolo AS, Curatoli FP. Corticosteroid therapy in the prevention of recurrent postsurgical nasal polyposis. Acta Otorhinolaryngologica Italica 1996;16(4):334–8. Chi Chan 1996 {published data only} Chi Chan A, Couto y Arcos F, Martin Biasotti F, Bross Soriano D, Vazquez Valle MDC, Gonzalez Olvera S. Oral steroids as preoperative medication in nasal polyposis [Esteroides orales en la preparacion preoperatoria de poliposis nasal]. Anales de Otorrinolaringologia Mexicana 1996;41(3):155–60. Damm 1999 {published data only} Damm M, Jungehulsing M, Eckel HE, Schmidt M, Theissen P. Effects of systemic steroid treatment in chronic polypoid rhinosinusitis evaluated with magnetic resonance imaging. Otolaryngology - Head and Neck Surgery 1999;120 (4):517–23. Hessler 2007 {published data only} Hessler JL, Piccirillo JF, Fang D, Vlahiotis A, Banerji A, Levitt RG, et al.Clinical outcomes of chronic rhinosinusitis in response to medical therapy: results of a prospective study. American Journal of Rhinology 2007;21(1):10–8. Jankowski 2003a {published data only} Jankowski R, Bodino C. Evolution of symptoms associated to nasal polyposis following oral steroid treatment and nasalisation of the ethmoid - radical ethmoidectomy is functional surgery for NPS. Rhinology 2003;41(4):211–9. Jankowski 2003b {published data only} Jankowski R, Bodino C. Olfaction in patients with nasal polyposis: effects of systemic steroids and radical ethmoidectomy with middle turbinate resection (nasalisation). Rhinology 2003;41(4):220–30. Kroflic 2006 {published data only} Kroflic B, Coer A, Baudoin T, Kalogjera L. Topical furosemide versus oral steroid in preoperative management of nasal polyposis. European Archives of Oto-RhinoLaryngology 2006;263(8):767–71.

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Lildholdt 1988 {published data only} Lildholdt T, Fogstrup J, Gammelgaard N, Kortholm B, Ulsoe C. Surgical versus medical treatment of nasal polyps. Acta Otolaryngologica 1988;105(1-2):140–3. Lildholdt 1989 {published data only} Lildholdt T. Surgical versus medical treatment of nasal polyps. Rhinology. Supplement 1989;8:31–3. Nores 2003 {published data only} Nores J-M, Avan P, Bonfils P. Medical management of nasal polyposis: a study in a series of 152 consecutive patients. Rhinology 2003;41(2):97–102. Ragab 2006 {published data only} Ragab SM, Lund VJ, Saleh HA, Scadding G. Nasal nitric oxide in objective evaluation of chronic rhinosinusitis therapy. Allergy 2006;61(6):717–24.

of response to oral and intranasal corticosteroid in nasal polyposis [completed]. ClinicalTrials.gov 2009 (accessed 31 October 2009). [: NCT00788749] ∗ Vaidyanathan S, Williamson P, Barnes M, Clearie K, Lipworth B. Influence of aspirin sensitivity and asthma on steroid response in nasal polyposis. Thorax: British Thoracic Society Winter Meeting, 3-5 December, 2008. 2008:Abstract S41.

Additional references Buchbinder 2006 Buchbinder R, Green S, Youd JM, Johnston RV. Oral steroids for adhesive capsulitis. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/ 14651858.CD006189]

Rasp 1997 {published data only} Rasp G, Bujia J. Treatment of nasal polyposis with systemic and local corticoids. Acta Otorrinolaringologica Espanola 1997;48(1):37–40.

Burton 2009 Burton JM, O’Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD006921.pub2]

Rasp 2000 {published data only} Rasp G, Kramer MF, Ostertag P, Kastenbauer E. A new system for the classification of ethmoid polyposis. Effect of combined local and systemic steroid therapy. LaryngoRhino-Otologie 2000;79(5):266–72.

Chalmers 1990 Chalmers I, Adams M, Dickersin K, Hetherington J, Tarnow-Mordi W, Meinert C, et al.A cohort study of summary reports of controlled trials. JAMA 1990;263: 1401–5.

Sieskiewicz 2006 {published data only} Sieskiewicz A, Olszewska E, Rogowski M, Grycz E. Preoperative corticosteroid oral therapy and intraoperative bleeding during functional endoscopic sinus surgery in patients with severe nasal polyposis: a preliminary investigation. Annals of Otology, Rhinology and Laryngology 2006;115(7):490–4.

Cheng 1999 Cheng K, Ashby D, Smyth RL. Oral steroids for cystic fibrosis. Cochrane Database of Systematic Reviews 1999, Issue 4. [DOI: 10.1002/14651858.CD000407]

Stevens 2001 {published data only} Stevens MH. Steroid-dependent anosmia. Laryngoscope 2001;111(2):200–3. Tuncer 2003 {published data only} Tuncer U, Soylu L, Aydogan B, Karakus F, Akcali C. The effectiveness of steroid treatment in nasal polyposis. Auris Nasus Larynx 2003;30(3):263–8. van Camp 1994 {published data only} van Camp C, Clement PA. Results of oral steroid treatment in nasal polyposis. Rhinology 1994;32(1):5–9. Van Zele 2008 {published data only} Van Zele T, Gevaert P, Holtappels G, Achim B, Wormald P, Mayr S, et al.American Academy of Allergy, Asthma and Immunology (AAAAI) 64th Annual Meeting. Philadelphia, PA, USA, March 14-18, 2008. Journal of Allergy and Clinical Immunology. 2008; Vol. 121(2 (Suppl 1)):S265, Abstract No. 1028.

References to ongoing studies Vaidyanathan 2009 {published data only (unpublished sought but not used)} Vaidyanathan S, Lipworth B. A proof of concept study to investigate the clinical, histological and molecular predictors

Drake-Lee 1984 Drake-Lee AB, Lowe D, Swanston A, Grace A. Clinical profile and recurrence of nasal polyps. Journal of Laryngology and Otology 1984;98:783–93. Drake-Lee 1997 Drake-Lee AB. Nasal polyps. In: Kerr AG, Mackay IS, Bull TR editor(s). Scott-Brown’s Otolaryngology. 6th Edition. Vol. 4: Rhinology, Oxford: Butterworth-Heinemann, 1997:4/10/1–16. Drake-Lee 2004 Drake-Lee AB. Nasal polyps. Hospital Medicine 2004;65: 264–7. EPOS 2007 Fokkens WJ, Lund VJ, Mullol J, on behalf of the European Position Paper on Rhinosinusitis and Nasal Polyps group. European Position Paper on Nasal Polyps. Rhinology 2007; 45(Suppl 20):1–139. Handbook 2009 Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2008. Available from www.cochrane-handbook.org. Larsen 1997 Larsen K, Tos M. A long-term follow-up study of nasal polyp patients after simple polypectomies. European Archives of Otorhinolaryngology 1997;254(Suppl 1):S85–8.

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Larsen 2004 Larsen PL, Tos M. Origin of nasal polyps: an endoscopic autopsy study. Laryngoscope 2004;114:710–9. Lund 1995 Lund VJ. Diagnosis and treatment of nasal polyps. BMJ 1995;311:1411–4. Mash 2001 Mash BRJ, Bheekie A, Jones P. Inhaled versus oral steroids for adults with chronic asthma. Cochrane Database of Systematic Reviews 2001, Issue 1. [DOI: 10.1002/ 14651858.CD002160] Mygind 1996 Mygind N, Lildholdt T. Nasal polyps treatment: medical management. Allergy and Asthma Proceedings 1996;17: 275–82. Nash 2011 Nash JJ, Nash AG, Leach ME, Poetker DM. Medical malpractice and corticosteroid use. Otolaryngology - Head and Neck Surgery 2011;144(1):10–5. Rajasekaran 2010 Rajasekaran K, Seth R, Abelson A, Batra PS. Prevalence of metabolic bone disease among chronic rhinosinusitis patients treated with oral glucocorticoids. American Journal of Rhinology and Allergy 2010;24(3):215–9.

Scadding 2002 Scadding GK. Comparison of medical and surgical treatment of nasal polyposis. Current Allergy and Asthma Reports 2002;2:494–9. Settipane 1977 Settipane GA, Chafee FH. Nasal polyps in asthma and rhinitis. A review of 6,037 patients. Journal of Allergy and Clinical Immunology 1977;59:17–21. Settipane 1996 Settipane GA. Epidemiology of nasal polyps. Allergy and Asthma Proceedings 1996;17:231–6. Stammberger 1999 Stammberger H. Surgical treatment of nasal polyps: past, present, and future. Allergy 1999;54(Suppl 53):7–11. Walters 2005 Walters JAE, Walters EH, Wood-Baker R. Oral corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD005374] Wei 2006 Wei BPC, Mubiru S, O’Leary S. Steroids for idiopathic sudden sensorineural hearing loss. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/ 14651858.CD003998.pub2] ∗ Indicates the major publication for the study

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CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID] Alobid 2006 Methods

Randomised: computer generation on a 1:3 ratio (explained by the main author when contacted) Allocation: not described Blinding: not described

Participants

78 patients with nasal polyps diagnosed endoscopically and radiologically Setting: hospital Country: Spain Mean age: 50 years (range 22 to 84 years) % female: 35 Number randomised: 80 participants (20 to control group but 2 lost to follow up) Aspirin sensitivity: 21% in treatment group; 6.4% in placebo group

Interventions

Group A: oral prednisone 30 mg daily for 4 days followed by a dose reducing by 5 mg every 2 days for 10 days Group B: no steroid treatment for 2 weeks

Outcomes

The following outcomes were measured immediately before treatment and at 2 weeks: nasal symptom score (unvalidated), polyp size score and quality of life assessment (Medical Outcome Study Short Form-36 (SF-36) questionnaire) Outcomes for the treatment group only (group A) were measured at 12, 24 and 48 weeks Adverse events: not reported, but main author when contacted reported there were no adverse effects in the trial

Notes

Two weeks after commencing oral steroid treatment, group A was commenced on treatment with intranasal budesonide and followed up but group B was not followed up as it was considered unethical not to offer known effective treatment to the control group for longer than 6 weeks Quality score: C

Risk of bias Bias

Authors’ judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

Randomisation using a computer-generated list on a 1:3 ratio

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Hissaria 2006 Methods

Randomised: participants were randomised by the hospital pharmacy, but the actual process is not described Allocation: not described Blinding: participants and study personnel were blinded.

Participants

41 patients drawn mainly from allergy outpatient clinics who had nasal polyps diagnosed endoscopically Setting: hospital Country: Australia Mean age: 49 years for treatment group and 48 years for placebo group (range 18 to 65 years) % female: 52 Number randomised: 41 participants (21 to control group but 1 lost to follow up) Aspirin sensitivity: 10% in treatment group; 30% in placebo group

Interventions

Treatment group: oral prednisone 50 mg daily for 14 days Placebo group: placebo for 14 days

Outcomes

The following outcomes were measured immediately before treatment and at 2 weeks: physician assessment on a VAS (1 to 5 score) including grading of nasal symptoms (6 scales: congestion, hyposmia, rhinorrhoea, sneezing, postnasal drip and itch); 6 nasal symptoms score on part of Rhinosinusitis Outcome Measure (RSOM-31) questionnaire, polyp size score on MRI and nasoendoscopy and quality of life assessment (total RSOM-31 score) Adverse events: reported in both treatment and control groups. The main adverse effect was insomnia (in 8 participants of the treatment group and 2 in the placebo group); mood disturbance (5 in treatment, 2 in placebo); and in fewer numbers of headache, dyspepsia, increased appetite, fatigue, backache, gastrointestinal disturbance, acne and feet oedema. There were no significant adverse effects

Notes

The study was not designed to look at long-term outcome Quality score: B

Risk of bias Bias

Authors’ judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B - Unclear

Van Zele 2010 Methods

Randomised: not described Allocation: not described Blinding: study personnel and participants were blinded for the duration of the study

Participants

47 patients recruited from 4 ear, nose and throat departments in Europe and 1 in Australia. Patients had recurrent nasal polyps after surgery or massive bilateral nasal polyps Setting: hospital Country: Europe (Belgium, The Netherlands, Germany) and Australia

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Van Zele 2010

(Continued)

Mean age: 49 years for steroid treatment group, 55 years for antibiotic treatment group and 55 years for placebo group (range 18 to 65 years) % female: 20 Number randomised: 47 participants (14 to each treatment group and 19 to placebo group but 7 lost to follow up in placebo group) Aspirin sensitivity: 14% in steroid treatment group; 7% in antibiotic group and 26% in placebo group Interventions

Steroid treatment group: oral methylprednisolone 32 mg daily for 5 days followed by a reducing dose to 16 mg daily for 5 days and 8 mg daily for 10 days (total 20 days) Antibiotic treatment group: oral doxycyline 200 mg on day 1, then 100 mg for 19 days (total 20 days) Placebo group: placebo for 20 days

Outcomes

The following outcomes were measured immediately before treatment and at 1, 2, 4, 8 and 12 weeks: total polyp score (0 to 4 for each nostril); peak nasal inspiratory flow (PNIF) measurement and nasal symptoms (anterior rhinorrhoea, nasal obstruction, postnasal drip and loss of sense of smell); eosinophil, IL-5 and eosinophilic cationic protein (ECP) counts in blood and; ECP, IgE, IL-5, matrix metallo-proteinase (MMP-9) and myeloperoxidase counts in nasal secretions Adverse events: reported 48.5% of the subjects in the study reported at least 1 adverse event. There were no significant differences of adverse events between the treatments and placebo groups

Notes

After week 4 from the start of the study 52% of the participants assigned to the placebo group underwent rescue treatment (either surgical or nasal steroids), 28% of the antibiotic treatment group needed rescue treatment and likewise 14% of the steroid treatment group. Therefore there was too large a number of dropouts in the study to assess long-term results in any group Quality score: C

Risk of bias Bias

Authors’ judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B - Unclear

MRI: magnetic resonance imaging RSOM: Rhinosinusitis Outcome Measure questionnaire VAS: visual analogue scale

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Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Alobid 2005

ALLOCATION Randomised; randomisation method not given PARTICIPANTS Nasal polyps diagnosed endoscopically and radiologically INTERVENTIONS Oral steroids versus endoscopic sinus surgery

Benitez 2006

ALLOCATION Randomised; randomisation method not given PARTICIPANTS Nasal polyps diagnosed endoscopically and radiologically INTERVENTIONS Oral steroids versus no treatment The study was excluded as possible duplication of Alobid 2006. Both studies were carried out in the same department and during the same period of time: February 1999 to July 2003 in Alobid 2006 with 78 participants and February 1999 to November 2003 in Benitez 2006 with 84 patients recruited. The patient characteristics were very similar. The main difference was in the outcome measures and the subgroups used in the second study (Benitez 2006) where the treatment group was also subdivided into patients with and without asthma. We asked the (same) corresponding author for both trials but they did not comment on this point

Blomqvist 2001

ALLOCATION Randomised; randomisation method not given PARTICIPANTS Nasal polyps diagnosed clinically and endoscopically INTERVENTIONS Oral steroids and topical steroids versus endoscopic sinus surgery and topical steroids

Blomqvist 2009

ALLOCATION Randomised; randomisation method not given PARTICIPANTS Nasal polyps diagnosed clinically and endoscopically INTERVENTIONS Oral steroids and topical steroids versus combined medical and surgical treatment

Bonfils 1998

ALLOCATION Non-randomised, no control group

Bonfils 2003

ALLOCATION Non-randomised, no control group

Bonfils 2006

ALLOCATION Non-randomised, no control group

Cassano 1996

ALLOCATION Non-randomised retrospective study

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(Continued)

Chi Chan 1996

ALLOCATION Non-randomised, no control group

Damm 1999

ALLOCATION Randomised; randomisation method not given PARTICIPANTS 20 patients (40 nasal cavities) with chronic polypoid rhinosinusitis - 80% of these patients (33 nasal cavities) had nasal polyps diagnosed radiologically INTERVENTIONS Group1: total dose of 560 mg oral fluocortolone 12 days Group 2: total dose of 715 mg oral fluocortolone for 20 days Reducing dose regimen in both groups OUTCOMES Trial rejected because data were not extractable. Change in MRI appearances were not reported separately for groups 1 and 2. Changes in symptom visual analogue scales were reported for Groups 1 and 2 in the chronic polypoid rhino-sinusitis patients but not for subset of patients with nasal polyps

Hessler 2007

ALLOCATION Non-randomised, no control group

Jankowski 2003a

ALLOCATION Non-randomised, no control group

Jankowski 2003b

ALLOCATION Non-randomised, no control group

Kroflic 2006

ALLOCATION Randomised; randomisation method not given PARTICIPANTS Nasal polyps diagnosed endoscopically and radiologically INTERVENTIONS Oral steroids versus topical furosemide OUTCOMES Trial rejected because only intraoperative surgical variables reported

Lildholdt 1988

ALLOCATION Randomised using computer-generated random figures PARTICIPANTS Method of diagnosing nasal polyps not given INTERVENTIONS Intramuscular steroid versus surgery

Lildholdt 1989

ALLOCATION Randomised using computer-generated random figures PARTICIPANTS Method of diagnosing nasal polyps not given INTERVENTIONS Surgical polypectomy followed by continuous topical steroid treatment versus a single dose of depot steroid

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(Continued)

followed by continuous topical steroid treatment Nores 2003

ALLOCATION Non-randomised, no control group

Ragab 2006

ALLOCATION Randomised; randomisation method not given PARTICIPANTS Chronic rhinosinusitis with or without nasal polyps diagnosed endoscopically and radiologically INTERVENTIONS Erythromycin, nasal douche and topical steroids versus surgery

Rasp 1997

ALLOCATION Non-randomised, no control group

Rasp 2000

ALLOCATION Non-randomised, no control group

Sieskiewicz 2006

ALLOCATION Randomised; randomisation method not given PARTICIPANTS Nasal polyps diagnosed clinically and radiologically INTERVENTIONS Oral steroids versus no intervention prior to endoscopic sinus surgery in both groups

Stevens 2001

ALLOCATION Non-randomised, no control group

Tuncer 2003

ALLOCATION Non-randomised, no control group

van Camp 1994

ALLOCATION Non-randomised, no control group

Van Zele 2008

Abstract of later publication: Van Zele 2010

MRI: magnetic resonance imaging

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Characteristics of ongoing studies [ordered by study ID] Vaidyanathan 2009 Trial name or title

A proof of concept study to investigate the clinical, histological and molecular predictors of response to oral and intranasal corticosteroid in nasal polyposis

Methods

Randomised, double-blind, controlled trial

Participants

60 adults 18 to 75 years of age

Interventions

Treatment group: oral prednisolone 25 mg daily for 2 weeks followed by fluticasone nasal drops 800 µg/day for 2 months followed by fluticasone nasal spray 400 µg/day for 4 months Placebo group: oral placebo daily for 2 weeks followed by fluticasone nasal drops 800 µg/day for 2 months followed by fluticasone nasal spray 400 µg/day for 4 months

Outcomes

Primary outcome measure: endoscopy polyp grading Secondary outcome measures: mini RQLQ, TNS-4, PNIF, anosmia score, scratch ’n’ sniff cards, OUCC, 1 µg synacthen test Measurements at 0, 2, 10 and 28 weeks

Starting date

May 2004

Contact information

Mr S Vaidyanathan and Dr B Lipworth, University of Dundee, UK

Notes

-

PNIF: peak nasal inspiratory flow RQLQ: Rhinitis Quality of Life Questionnaire

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DATA AND ANALYSES This review has no analyses.

APPENDICES Appendix 1. Search strategies

CENTRAL

PubMed

EMBASE (Ovid)

CINAHL (EBSCO)

#1 NASAL POLYPS single term (MeSH) #2 POLYPS explode all trees (MeSH) #3 (polyp* OR papilloma*) #4 NOSE explode all trees (MeSH) #5 (nose* OR nasal* OR nasi OR intranasal* OR sinonasal* OR paranasal*) #6 (#2 OR #3) #7 (#4 OR #5) #8 (#6 AND #7) #9 rhinopolyp* #10 (#1 OR #8 OR #9) #11 STEROIDS explode all trees (MeSH) #12 ADRENAL CORTEX HORMONES explode all trees (MeSH) #13 GLUCOCORTICOIDS explode all trees (MeSH) #14 (steroid* OR glucocorticoid* OR corticosteroid* OR glucosteroid* OR cyclocosteroid*) #15 (beclomethasone OR beclometasone OR beclamet OR beclocort OR becotide) #16 (betamethasone OR betadexamethasone OR flubenisolone OR celeston* OR cellestoderm OR betnelan OR oradexon) #17 (dexamethasone OR dexameth OR dexone OR dexam-

#1 “NASAL POLYPS” [Mesh] OR rhinopolyp* [tiab] #2 “POLYPS” [Mesh] OR POLYP* [tiab] OR PAPILLOMA* [tiab] #3 “NOSE” [Mesh] OR NOSE* [tiab] OR NASAL* [tiab] OR NASI [tiab] OR INTRANASAL* [tiab] OR SINONASAL* [tiab] OR PARANASAL* [tiab] #4 #1 OR (#2 AND #3) #5 “STEROIDS” [Mesh] OR “ADRENAL CORTEX HORMONES” [Mesh] OR “GLUCOCORTICOIDS” [Mesh] #6 STEROID*[tiab] OR GLUCOCORTICOID*[tiab] OR CORTICOSTEROID*[tiab] OR GLUCOSTEROID*[tiab] OR CYCLOSTEROID*[tiab] #7 BECLOMETASONE[tiab] OR BECLAMET[tiab] OR BECLOCORT[tiab] OR BECOTIDE[tiab] OR BETADEXAMETHASONE[tiab] OR FLUBENISOLONE[tiab] OR CELESTON$1[tiab] OR CELLESTODERM[tiab] OR BETNELAN[tiab] OR DEXAMETH[tiab] OR DEXONE[tiab] OR DEXAMETASONE[tiab] OR DECADRON[tiab]

1 nose polyp/ 2 polyp/ or polyposis/ 3 (polyp* or papillom*).tw. 4 2 or 3 5 exp *nose/ 6 (NOSE* or NASAL* or NASI or INTRANASAL* or SINONASAL* or PARANASAL*).tw. 7 5 or 6 8 4 and 7 9 rhinopolyp*.tw. 10 1 or 8 or 9 11 exp Corticosteroid/ 12 (STEROID* or GLUCOCORTICOID* or CORTICOSTEROID* or GLUCOSTEROID* or CYCLOSTEROID*).tw. 13 (BECLOMETASONE or BECLAMET or BECLOCORT or BECOTIDE or BETADEXAMETHASONE or FLUBENISOLONE or CELESTON* or CELLESTODERM or BETNELAN or DEXAMETH or DEXONE or DEXAMETASONE or DECADRON or DEXASONE or HEXADECADRON or HEXADROL or ETHYLFLU ORPREDNISOLONE or MILLIC ORTEN or ORADEXON or CORTISOL or CORTI-

S1 (MH “Nasal Polyps”) S2 (MH “Polyps+”) S3 TX polyp* OR papilloma* S4 S2 or S3 S5 (MH “Nose+”) S6 TX NOSE* or NASAL* or NASI or INTRANASAL* or SINONASAL* or PARANASAL* S7 S5 or S6 S8 S4 and S7 S9 TX rhinopolyp* S10 S1 or S8 or S9 S11 (MH “Steroids+”) S12 (MH “Glucocorticoids”) S13 (MH “Adrenal Cortex Hormones+”) S14 TX STEROID* or GLUCOCORTICOID* or CORTICOSTEROID* or GLUCOSTEROID* or CYCLOSTEROID* S15 TX BECLOMETASONE or BECLAMET or BECLOCORT or BECOTIDE or BETADEXAMETHASONE or FLUBENISOLONE or CELESTON* or CELLESTODERM or BETNELAN or DEXAMETH or DEXONE or DEXAMETASONE or DECADRON or DEXASONE or HEXADECADRON or HEX-

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(Continued)

etasone OR decadron OR dexasone OR hexadecadron OR hexadrol OR methylfluorprednisolone OR millicorten) #18 (flunisolide OR fluticasone OR hydrocortisone OR cortisol OR cortifair OR cortril OR hyrocortone OR cortef OR epicortisol OR efcortesol) #19 (methylprednisolone OR medrol OR metripred OR urbason) #20 (mometasone OR prednisolone OR precortisyl OR deltacortril OR deltastab OR prednesol OR deltasone OR prednisone OR cortan OR liquid NEXT pred OR meticorten) #21 (paramethasone OR triamcinolone OR aristocort OR volon OR atolone OR kenacort OR orasone OR panasol OR prednicen) #22 (#11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 or #18 or #19 or #20 or #21) #23 (#10 AND #22)

OR DEXASONE[tiab] OR HEXADECADRON[tiab] OR HEXADROL[tiab] OR ETHYLFLU[tiab] ORPREDNISOLONE[tiab] OR MILLIC[tiab] ORTEN[tiab] OR[tiab] ORADEXON[tiab] OR CORTISOL[tiab] OR CORTIFAIR[tiab] OR CORTRIL[tiab] OR HYROCORTONE[tiab] OR CORTEF[tiab] OR EPICORTISOL[tiab] OR EFCORTESOL[tiab] OR MEDROL[tiab] OR METRIPRED[tiab] OR URBASON[tiab] OR MOMETASONE[tiab] OR PRECORTISYL[tiab] OR DELTACORTRIL[tiab] OR DELTASTAB[tiab] OR PREDNESOL[tiab] OR DELTASONE[tiab] OR CORTAN[tiab] OR “LIQUID PRED”[tiab] OR METICORTEN[tiab] OR ORASONE[tiab] OR PANASOL[tiab] OR PREDNICEN [tiab] #8 PARAMETHASONE[tiab] OR ARISTOCORT[tiab] OR VOLON[tiab] OR ATOLONE[tiab] OR KENACORT[tiab] OR BECLOMETHASONE[tiab] OR 4419-39-0[tiab] OR BETAMETHASONE[tiab] OR 378-44-9 [tiab] OR BUDESONIDE[tiab] OR 51333-22-3 [tiab] OR CORTISONE[tiab] OR 53-06-5[tiab] OR DEXAMETHASONE[tiab] OR 50-02-2 [tiab] OR FLUNISOLIDE[tiab] OR 3385-03-3[tiab] OR FLUTICASONE[tiab] OR 9056653-3[tiab] OR “FLUTICASONE PROPIONATE” [tiab]

FAIR or CORTRIL or HYROCORTONE or CORTEF or EPICORTISOL or EFCORTESOL or MEDROL or METRIPRED or URBASON or MOMETASONE or PRECORTISYL or DELTACORTRIL or DELTASTAB or PREDNESOL or DELTASONE or CORTAN or (LIQUID adj PRED) or METICORTEN or ORASONE or PANASOL or PREDNICEN). tw. 14 (PARAMETHASONE or ARISTOCORT or VOLON or ATOLONE or KENACORT or BECLOMETHASONE or 4419-39-0 or BETAMETHASONE or 378-44-9 or BUDESONIDE or 51333-22-3 or CORTISONE or 53-06-5 or DEXAMETHASONE or 50-02-2 or FLUNISOLIDE or 338503-3 or FLUTICASONE or 90566-53-3 or (FLUTICASONE adj PROPIONATE) or 80474-14-2 or HYDROCORTISONE or CORTISOL or 50-23-7 or METHYLPREDNISOLONE or 83-43-2 or MOMETASONE or 10510222-5 or PREDNISOLONE or 50-24-8 or PREDNISONE or 53-03-2 or TRIAMCINOLONE or 124-94-7).tw. 15 11 or 12 or 13 or 14 16 10 and 15

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ADROL or ETHYLFLU ORPREDNISOLONE or MILLIC ORTEN or ORADEXON or CORTISOL or CORTIFAIR or CORTRIL or HYROCORTONE or CORTEF or EPICORTISOL or EFCORTESOL or MEDROL or METRIPRED or URBASON or MOMETASONE or PRECORTISYL or DELTACORTRIL or DELTASTAB or PREDNESOL or DELTASONE or CORTAN or (LIQUID adj PRED) or METICORTEN or ORASONE or PANASOL or PREDNICENTX BECLOMETASONE or BECLAMET or BECLOCORT or BECOTIDE or BETADEXAMETHASONE or FLUBENISOLONE or CELESTON* or CELLESTODERM or BETNELAN or DEXAMETH or DEXONE or DEXAMETASONE or DECADRON or DEXASONE or HEXADECADRON or HEXADROL or ETHYLFLU ORPREDNISOLONE or MILLIC ORTEN or ORADEXON or CORTISOL or CORTIFAIR or CORTRIL or HYROCORTONE or CORTEF or EPICORTISOL or EFCORTESOL or MEDROL or METRIPRED or URBASON or MOMETASONE or PRECORTISYL or DELTACORTRIL or DELTASTAB or PREDNESOL or DELTASONE or S16 TX PARAMETHASONE or ARISTOCORT or VOLON or ATOLONE or KENA-

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(Continued)

OR 80474-14-2[tiab] OR HYDROCORTISONE[tiab] OR CORTISOL[tiab] OR 50-237[tiab] OR METHYLPREDNISOLONE[tiab] OR 83-43-2 [tiab] OR MOMETASONE[tiab] OR 105102-22-5 [tiab] OR PREDNISOLONE[tiab] OR 50-248 [tiab] OR PREDNISONE[tiab] OR 53-03-2[tiab] OR TRIAMCINOLONE[tiab] OR 124-94-7 [tiab] #9 #5 OR #6 OR #7 OR #8 #10 #4 AND #9

CORT or BECLOMETHASONE or 4419-39-0 or BETAMETHASONE or 378-449 or BUDESONIDE or 5133322-3 or CORTISONE or 5306-5 or DEXAMETHASONE or 50-02-2 or FLUNISOLIDE or 3385-03-3 or FLUTICASONE or 90566-53-3 or (FLUTICASONE adj PROPIONATE) or 80474-14-2 or HYDROCORTISONE or CORTISOL or 50-23-7 or METHYLPREDNISOLONE or 83-43-2 or MOMETASONE or 10510222-5 or PREDNISOLONE or 50-24-8 or PREDNISONE or 53-03-2 or TRIAMCINOLONE or 124-94-7 S17 S11 or S12 or S13 or S14 or S15 or S16 S18 S10 and S17

Web of Science/ BIOSIS Pre- ISRCTN (mRCT) views (Web of Knowledge)

CAB Abstracts (Ovid)

Cochrane Ear, Nose and Throat Disorders Group Trials Register

#1 TS=(nose OR nasal* OR (nose OR nasal) AND (polyp% paranasal* OR sinonasal* OR OR papillom%) intranasal*) AND (polyp* OR papillom*)) OR rhinopolyp*) #2 TS=(STEROID* or GLUCOCORTICOID* or CORTICOSTEROID* or GLUCOSTEROID* or CYCLOSTEROID*) #3 TS=(BECLOMETASONE or BECLAMET or BECLOCORT or BECOTIDE or BETADEXAMETHASONE or FLUBENISOLONE or CELESTON* or CELLESTODERM or BETNELAN or DEXAMETH or DEXONE or DEXAMETASONE or DECADRON or DEXASONE or HEXADECADRON or HEX-

1 (polyp* or papillom*).tw. 2 (NOSE* or NASAL* or NASI or INTRANASAL* or SINONASAL* or PARANASAL*).tw. 3 1 AND 2 4 rhinopolyp*.tw. 5 3 OR 4 6 exp Corticosteroid/ 7 (STEROID* or GLUCOCORTICOID* or CORTICOSTEROID* or GLUCOSTEROID* or CYCLOSTEROID*).tw. 8 (BECLOMETASONE or BECLAMET or BECLOCORT or BECOTIDE or BETADEXAMETHASONE or FLUBENISOLONE or CELESTON* or CELLESTODERM or BETNELAN or DEXAM-

( (nose OR nasal* OR paranasal* OR sinonasal* OR intranasal*) AND (polyp* OR papillom*) ) AND (STEROID* or GLUCOCORTICOID* or CORTICOSTEROID* or GLUCOSTEROID* or CYCLOSTEROID*)

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(Continued)

ADROL or ETHYLFLU ORPREDNISOLONE or MILLIC ORTEN or ORADEXON or CORTISOL or CORTIFAIR or CORTRIL or HYROCORTONE or CORTEF or EPICORTISOL or EFCORTESOL or MEDROL or METRIPRED or URBASON or MOMETASONE or PRECORTISYL or DELTACORTRIL or DELTASTAB or PREDNESOL or DELTASONE or CORTAN or (LIQUID adj PRED) or METICORTEN or ORASONE or PANASOL or PREDNICEN) #4 TS=(PARAMETHASONE or ARISTOCORT or VOLON or ATOLONE or KENACORT or BECLOMETHASONE or 4419-39-0 or BETAMETHASONE or 378-449 or BUDESONIDE or 5133322-3 or CORTISONE or 5306-5 or DEXAMETHASONE or 50-02-2 or FLUNISOLIDE or 3385-03-3 or FLUTICASONE or 90566-53-3 or (FLUTICASONE adj PROPIONATE) or 80474-14-2 or HYDROCORTISONE or CORTISOL or 50-23-7 or METHYLPREDNISOLONE or 83-43-2 or MOMETASONE or 10510222-5 or PREDNISOLONE or 50-24-8 or PREDNISONE or 53-03-2 or TRIAMCINOLONE or 124-94-7) #5 #4 OR #3 OR #2 #6 #5 AND #1

ETH or DEXONE or DEXAMETASONE or DECADRON or DEXASONE or HEXADECADRON or HEXADROL or ETHYLFLU ORPREDNISOLONE or MILLIC ORTEN or ORADEXON or CORTISOL or CORTIFAIR or CORTRIL or HYROCORTONE or CORTEF or EPICORTISOL or EFCORTESOL or MEDROL or METRIPRED or URBASON or MOMETASONE or PRECORTISYL or DELTACORTRIL or DELTASTAB or PREDNESOL or DELTASONE or CORTAN or (LIQUID adj PRED) or METICORTEN or ORASONE or PANASOL or PREDNICEN). tw. 9 (PARAMETHASONE or ARISTOCORT or VOLON or ATOLONE or KENACORT or BECLOMETHASONE or 4419-39-0 or BETAMETHASONE or 378-44-9 or BUDESONIDE or 51333-22-3 or CORTISONE or 53-06-5 or DEXAMETHASONE or 50-02-2 or FLUNISOLIDE or 338503-3 or FLUTICASONE or 90566-53-3 or (FLUTICASONE adj PROPIONATE) or 80474-14-2 or HYDROCORTISONE or CORTISOL or 50-23-7 or METHYLPREDNISOLONE or 83-43-2 or MOMETASONE or 10510222-5 or PREDNISOLONE or 50-24-8 or PREDNISONE or 53-03-2 or TRIAMCINOLONE or 124-94-7).tw. 10 7 OR 8 OR 9 11 5 AND 10

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WHAT’S NEW Last assessed as up-to-date: 11 October 2010.

Date

Event

Description

17 February 2011

New search has been performed

We ran full new searches in October 2010.

17 February 2011

New citation required and conclusions have changed

We included two new studies (Hissaria 2006; Van Zele 2010) and excluded a further nine. The review conclusions have been strengthened. High-quality studies with long-term follow up are still necessary

HISTORY Protocol first published: Issue 2, 2005 Review first published: Issue 1, 2007

Date

Event

Description

26 October 2008

Amended

Converted to new review format.

CONTRIBUTIONS OF AUTHORS Pablo Martinez-Devesa: co-ordination of the review, screening search results, screening retrieved papers against inclusion criteria and editing of review, writing to authors of papers for additional information and writing of review. Shalini Patiar: co-ordination of review, screening search results, organising retrieval of papers, screening retrieved papers against inclusion criteria, writing to authors of papers for additional information, writing to experts in field and writing of review.

DECLARATIONS OF INTEREST None known.

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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SOURCES OF SUPPORT Internal sources • None, Not specified.

External sources • None, Not specified.

DIFFERENCES BETWEEN PROTOCOL AND REVIEW We added the secondary outcome measure ’Improvement in validated quality of life measures’.

INDEX TERMS Medical Subject Headings (MeSH) Administration, Oral; Nasal Obstruction [etiology]; Nasal Polyps [complications; ∗ drug therapy]; Olfaction Disorders [etiology]; Prednisone [∗ administration & dosage]; Randomized Controlled Trials as Topic; Steroids [∗ administration & dosage]

MeSH check words Humans

Oral steroids for nasal polyps (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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